C-peptide Attenuates Progression of Atherosclerosis in Late Stages of Type 2 Diabetes in Male Albino Rats

Abstract

Aims: Study the role of C-peptide in development of atherosclerosis in late stages of type 2 diabetes in rats. Methodology: Late stages of type II diabetes were induced by administeration of high fat diet and intraperitoneal injection of a single dose of streptozotocin 35 mg/kg,  then rats were divided into 5 groups: 1) control, 2) Diabetic (DM), 3) Diabetic + C-peptide, 4) Diabetic + L-NAME, and 5) Diabetic + C-peptide + L-NAME. Measurements: At the end of the experiment blood samples were taken for measurement of serum glucose and insulin levels. The arch of the aorta was taken for: Histopathological study and measurement of tissue lipid peroxides (MDA), Bcl-2 (B-cell lymphoma protein 2, apoptotic factor), nitric oxide (NO) and tumor necrosis factor-α (TNF-α). Results: Aorta of diabetic rats showed severe atherosclerotic changes, and there were significant increase in serum glucose, tissue MDA, and TNF-α alongside there were significant decrease in serum insulin, tissue NO and Bcl-2 as compared to control group. Significant improvement in atherosclerotic changes were observed in Diabetic + C-peptide group which was accompanied with significant decrease in serum glucose, tissue MDA, and TNF-α. There were also significant increase in serum insulin and tissue NO and Bcl-2 as compared to DM group. In DM + L-NAME group, there were severe deterioration of atherosclerotic changes, and there were significant increase in serum glucose, tissue MDA, and TNF-α alongside significant decrease in serum insulin, tissue NO and Bcl-2 as compared to DM group. Although adding L-NAME to DM + C-peptide group abolished increasing in serum insulin level but improvement in atherosclerotic changes and other parameters were still present. Conclusion: C-peptide has a protective effect against development of atherosclerosis through many mechanisms including hypoglycemic, antioxidant, antiapoptotic, and anti-inflammatory effects. So administration of C-peptide as an adjuvant therapy in late stages of type II diabetes can significantly decrease incidence of vasculopathy.